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RAPID ANTI-INFLAMMATORY EFFECT OF INHALED CICLESONIDE IN ASTHMA: A RANDOMISED, PLACEBO-CONTROLLED STUDY

^aNational Heart and Lung Institute Clinical Studies Unit, Imperial College, London, United Kingdom (e.erin@imperial.ac.uk; g.nicholson@imperial.ac.uk; a.tan@imperial.ac.uk; h.neighbour@imperial.ac.uk; t.hansel@imperial.ac.uk) ^bDepartment of Pediatric and Adolescent Medicine, Pulmonary and Infectious Diseases, Wilhelminenspital, Vienna, Austria (angela.zacharasiewicz@wienkav.at) ^cNycomed GmbH, Konstanz, Germany (renate.engelstaetter@altanapharma.com; michael.hellwig@altanapharma.com) ^dSt Mary's Hospital, Paddington, London (onn.kon@st-marys.nhs.uk) ^eDepartment of Thoracic Medicine, Imperial College, London, United Kingdom (p.j.barnes@imperial.ac.uk)

Abstract

Background: Ciclesonide is a novel inhaled corticosteroid for the treatment of asthma, and it is important to measure the onset of effect of this therapy on airway hyperresponsiveness (AHR), exhaled nitric oxide (NO) and induced sputum inflammatory biomarkers.

Methods: In a randomised, double-blind, crossover study, 21 patients with mild asthma inhaled ciclesonide 320 µg (ex-actuator) once daily, ciclesonide 640 µg (ex-actuator) twice daily and placebo for 7 days. Exhaled NO and AHR to adenosine monophosphate (AMP), measured as the provocative concentration of AMP producing a 20% reduction in forced expiratory volume in 1 second (PC₂₀FEV₁), were assessed after inhalation on Days 1, 3 and 7. Sputum was assayed for chemokine and cytokine levels.

Results: Ciclesonide 320 µg once daily and 640 µg twice daily produced significantly greater improvements in PC₂₀FEV₁ compared with placebo on Day 1 (within 2.5 hours), and on Days 3 and 7 (all p<0.0001). On Day 3, both ciclesonide doses significantly reduced exhaled NO levels by –17.7 (p<0.0001) and –15.4 parts per billion (p<0.003) versus placebo, respectively. Significant reductions were maintained during the study with both ciclesonide doses (p<0.01). Sputum interleukin-1, -6, -8 and -12 were significantly (p0.01) inhibited by ciclesonide 640 µg twice daily within 4 hours; effects were maintained during the study.

Conclusions: A single dose of ciclesonide decreased AHR to AMP within hours, and decreased chemokine and cytokine levels in sputum. There was also a constant decrease in exhaled NO during the study. ClinicalTrials.gov Study ID Number BY9010/M1-125.

Key Words: Ciclesonide • airway hyperresponsiveness • sputum • nitric oxide • asthma